New Update Changes Terminology for Some Cutaneous Lymphomas

The terminology of some cutaneous lymphoids was updated in the 2022 International Consensus Classification of lymphomas (2022ICC), according to a recent review published in Virchows Archiv: European Journal of Pathology. Understanding the pathogenesis of these diseases, along with having a better classification of different lymphoma types, can improve the potential for targeted therapies and help predict patient responses, according to the study authors.

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“Accurate diagnosis of the cutaneous lymphomas is essential in view of the broad range of clinical behavior they exhibit, including lesions that spontaneously regress, lymphoid proliferations that that persist but pursue an indolent course and rapidly progressing aggressive malignancies that are often fatal,” the authors wrote in the review.

Investigators conducted the review to discuss revisions in the nomenclature and classification of cutaneous lymphomas. They also highlight findings from new genomic studies that propel understanding of the disease and outline possible drug targets.

One of the main updates in terminology was downgrading primary cutaneous marginal zone lymphoma from an extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) to a lymphoproliferative disorder—generally called primary cutaneous marginal zone lymphoproliferative disorder (PCMZLPD). This is because the disease was less active than other lymphomas and patients were having better prognoses, according to the investigators.

There are now 2 subtypes of PCMZLPD that can be classified based on the lymphoma being heavy chain class-switched or immunoglobulin M (IgM)-positive. IgM-positive disease usually involves the deep dermal layer (subcutis), which contains neoplastic B cells expressing the immunoglobulin superfamily receptor translocation-associated 1 (IRTA1) and C-X-C motif chemokine receptor 3 (CXCR3) receptors.

A second lymphoma that will now be classified as a lymphoproliferative disorder is primary cutaneous acral CD8-positive T cell lymphoma. Primary cutaneous follicle center lymphoma will continue to be classified as a lymphoma. The disease—identifiable by localized plaques, nodules or tumors on the head, neck, scalp, or trunk—is still associated with significant incidence of disease spread outside of the skin and lymphoma-related deaths still occur.

Understanding the genetic, epigenetic, and transcriptional changes in lymphomas could help with identifying novel therapy targets. For instance, new therapies for cutaneous T-cell lymphomas could target the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway.

Primary cutaneous lymphomas and lymphoproliferative disorders are both cutaneous lymphoid neoplasms that have not affected any organ outside of the skin (extracutaneous). Although cutaneous lymphomas are similar to other lymphomas, these usually start at the lymph nodes before affecting the skin.

Classifying cutaneous lymphomas remains a challenge, but advanced technology is helping to improve insight into the pathology. There are currently candidate drugs used for hematologic malignancies that could be used for lymphomas, and understanding how lymphomas respond to treatment will help with their categorization.

The authors concluded, “[These studies] not only identify potential targets for novel therapies, but also raise as yet unanswered questions as to how we categories cutaneous lymphomas, particularly with respect to relationships with similar lymphomas at extracutaneous sites.”

Reference

Goodlad J, Cerroni L, Swerdlow S. Recent advances in cutaneous lymphoma—implications for current and future classifications. Virchows Arch 482, 281–298 (2023). DOI:10.1007/s00428-022-03421-5.